Status:
COMPLETED
Study to Assess the Incidence of Hemolysis, Safety, and Efficacy of Tafenoquine (SB-252263, WR238605) Versus Primaquine in Subjects With Plasmodium Vivax Malaria
Lead Sponsor:
GlaxoSmithKline
Collaborating Sponsors:
Medicines for Malaria Venture
Conditions:
Malaria, Vivax
Eligibility:
All Genders
16+ years
Phase:
PHASE3
Brief Summary
This is a prospective, double-blind, double-dummy, multicenter, comparative study. A total of 300 subjects will be randomized to treatment on Day 1, of which a minimum of 50 female subjects must be en...
Eligibility Criteria
Inclusion
- A female is eligible to enter and participate in the study if she is non-pregnant, nonlactating and if she is of: a. Non-childbearing potential defined as: post-menopausal (12 months of spontaneous amenorrhea or \<6 months of spontaneous amenorrhea with serum follicle-stimulating hormone \>40 milli-International units per milliliter \[mIU/mL\]), or pre-menopausal and has had a hysterectomy or a bilateral oophorectomy (removal of the ovaries) or a bilateral tubal ligation, negative pregnancy test or, b. Child-bearing potential, has a negative pregnancy test at screening, and agrees to comply with one of the following during the treatment stage of the study and for a period of 90 days after stopping study medication: Use of oral contraceptive, either combined or progestogen alone used in conjunction with double barrier method as defined below. Use of an intrauterine device with a documented failure rate of \<1% per year; Use of depo provera injection; Double barrier method consisting of spermicide with either condom or diaphragm; Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female. Complete abstinence from intercourse for 2 weeks prior to administration of study medication, throughout the study and for a period of 90 days after stopping study medication.
- The subject has a glucose 6-phosphate dehydrogenase (G6PD) value (measured by a quantitative spectrophotometric phenotype assay) as follows: Female subjects must have an enzyme level \>= 40 percent of the site median value for G6PD normal males. Male subjects must have an enzyme level \>= 70 percent of the site median value for G6PD normal males.
- The subject has a screening hemoglobin (Hb) value as follows: Any subject with a G6PD value \>=70 percent of the site median value must have a screening Hb value \>=7 g/dL; Female subjects with a G6PD value is \>=40 - \<70 percent of the site median value must have a screening Hb value \>=8 g/dL.
- The subject has a QT duration corrected for heart rate by Fridericia's Formula (QTcF) \<450 milisecond (msec). Reading based on an average of triplicate Electrocardiograms (ECGs) obtained over a brief recording period by machine or manual over-read.
- The subject has a positive malarial smear for P. vivax .
- The subject has a parasite density of \>100 and \<100,000 per microliter (μL).
- Male or female subject aged 16 years or older (18 years or older in Ethiopia) at the time of signing the informed consent.
- The subject agrees to G6PD genotyping.
- The subject is willing and able to comply with the study protocol.
- The subject or parent/legal guardian, as applicable, has given written informed, dated consent; and the subject has given written assent, if applicable, to participate in the study.
Exclusion
- The subject has a mixed malaria infection (identified by a malarial smear or rapid diagnostic test).
- The subject has severe P. vivax malaria as defined by World Health Organization (WHO) criteria.
- The subject has a history of allergy to chloroquine, mefloquine, tafenoquine, primaquine, or to any other 4- or 8-aminoquinoline.
- The subject has a liver alanine aminotransferase (ALT) \>2 x upper limit of normal (ULN).
- The subject has severe vomiting (no food or inability to take food during the previous 8 hours).
- The subject has a clinically significant concurrent illness (e.g., pneumonia, septicemia), pre-existing condition (e.g., renal disease, malignancy), condition that may affect absorption of study medication (e.g., vomiting, severe diarrhea), or clinical signs and symptoms of severe cardiovascular disease (e.g., uncontrolled congestive heart failure, severe coronary artery disease).
- The subject has a history of porphyria, psoriasis, or epilepsy.
- The subject has a history of significant ocular disease (e.g. surgery to the globe, glaucoma, diabetic retinopathy) or has evidence of corneal or retinal abnormalities identified in the clinical screening ophthalmologic examination.
- The subject has taken anti-malarials (e.g., artemisinin-based combination therapies, mefloquine, primaquine, or any other 4- or 8-aminoquinoline) within 30 days prior to study entry.
- The subject has taken or will likely require during the study the use of medications from the following classes: Histamine-2 blockers and antacids; Drugs with hemolytic potential; Drugs known to prolong the QTcF interval; The biguanides phenformin and buformin (but excluding metformin); Drugs that are substrates of the renal transporters OCT2, MATE1 AND MATE-2K and have a narrow therapeutic index (for example, the anti-arrhythmic agents dofetilide, procainamide and pilsicainide)
- The subject has received treatment with any investigational drug within 30 days of study entry, or within 5 half-lives, whichever is longer.
- The subject has a recent history of illicit drug abuse or heavy alcohol intake, such that full participation in the study could be compromised.
Key Trial Info
Start Date :
April 30 2015
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
November 4 2016
Estimated Enrollment :
251 Patients enrolled
Trial Details
Trial ID
NCT02216123
Start Date
April 30 2015
End Date
November 4 2016
Last Update
May 16 2018
Active Locations (10)
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1
GSK Investigational Site
Manaus, Amazonas, Brazil, 69040-000
2
GSK Investigational Site
Cali, Colombia
3
GSK Investigational Site
Montería, Colombia
4
GSK Investigational Site
Gonder, Ethiopia